The specific ionic composition of the cytosol usually differs greatly from that of the surrounding extracellular fluid. In virtu ally all cells—including microbial, plant, and animal cells—the cytosolic pH is kept near 7.2 regardless of the extracellular pH.
In the most extreme case, there is a 1-million-fold difference in H+ concentration between the cytosol of the epithelial cells lining the stomach and the stomach contents after a meal. Furthermore, the cytosolic concentration of K+ is much higher than that of Na+. In both invertebrates and vertebrates, the concentration of K+ is 20–40 times higher in the cytosol than in the blood, while the concentration of Na+ is 8–12 times lower in the cytosol than in the blood (Table 1).
Table1. Typical Intracellular and Extracellular Ion Concentrations
Some Ca2+ in the cytosol is bound to the negatively charged groups in ATP and in proteins and other molecules, but it is the concentration of unbound (or “free”) Ca2+ that is critical to its functions in signaling pathways and muscle contraction. The concentration of free Ca2+ in the cytosol is generally less than 0.2 micromolar (2 × 10−7 M), a thousand or more times lower than that in the blood. Plant cells and many microorganisms maintain similarly high cytosolic concentrations of K+ and low concentrations of Ca2+ and Na+, even if the cells are cultured in very dilute salt solutions.
The ion pumps discussed in this section are largely re sponsible for establishing and maintaining the usual ionic gradients across the plasma and intracellular membranes. In carrying out this task, cells expend considerable energy. For example, up to 25 percent of the ATP produced by nerve and kidney cells is used for ion transport, and human erythrocytes consume up to 50 percent of their available ATP for this purpose; in both cases, most of this ATP is used to power the Na+/K+ pump (see Figure 1). The resultant Na+ and K+ gradients in neurons are essential for their ability to con duct electrical signals rapidly and efficiently. Certain enzymes required for protein synthesis in all cells require a high K+ concentration and are inhibited by high concentrations of Na+; these enzymes would cease to function without the operation of the Na+/K+ pump. In cells treated with poisons that inhibit the production of ATP (e.g., 2,4-dinitrophenol in aerobic cells), the pumping stops, and the ion concentrations inside the cell gradually approach those of the exterior environment as ions spontaneously move through channels in the plasma membrane down their electrochemical gradients. Eventually the treated cells die, partly because protein synthesis requires a high concentration of K+ ions and partly because, in the absence of a Na+ gradient across the plasma membrane, a cell cannot import certain nutrients such as amino acids (see Figure 1). Studies on the effects of such poisons provided early evidence for the existence and significance of ion pumps.
Fig1. Multiple membrane transport proteins function together in the plasma membrane of metazoan cells. Gradients are indicated by triangles with the tip pointing toward lower con centration. The Na+/K+ ATPase in the plasma membrane uses energy released by ATP hydrolysis to pump Na+ (red circles) out of the cell and K+ (blue squares) inward; this creates a concentration gradient of Na+ that is greater outside the cell than inside, and one of K+ that is greater inside than outside. Movement of positively charged K+ ions out of the cell through membrane K+ channels creates an electric potential across the plasma membrane—the cytosolic face is negative with respect to the extracellular face. A Na+/lysine transporter, a typical sodium/amino acid cotransporter, moves two Na+ ions together with one lysine from the extracellular medium into the cell. “Uphill” movement of the amino acid is powered by “downhill” movement of Na+ ions, which in turn is powered both by the outside-greater-than-inside Na+ concentration gradient and by the negative charge on the inside of the plasma mem brane, which attracts the positively charged Na+ ions. The ultimate source of the energy to power amino acid uptake comes from the ATP hydrolyzed by the Na+/K+ ATPase, since this pump creates both the Na+ ion concentration gradient and, via the K+ channels, the mem brane potential, which together power the influx of Na+ ions.
